1. Field of the Invention
The invention relates to a novel optically active aminopentane derivative, (xe2x88x92)-1-(benzofuran-2-yl)-2-propylaminopentane, which contains substantially no (+)-isomer, and to the pharmaceutically acceptable acid salts thereof. These are promising as active compounds of a pharmaceutical composition, especially, psychotropic composition, antidepressant, composition for treating Parkinson""s disease and/or Alzheimer""s disease.
2. Description of the Related Art
The ethylamine derivatives are known to have various biological actions. Particularly, aromatic ethylamine derivatives are thought to be hopeful as psychotropic composition, because they have the releasing action of displacing catecholamines from their storage places in the central nervous system. However, it is pointed out that these compositions have stimulant-like side effects such as neurotoxicity and abnormal behavior, because they easily cause excess catecholamine release from storage places, i.e. synaptic vesicles and so on. The continuous administration of these compositions, which enhance the excess catecholamine release, induces the decrease of catecholamine receptors. Consequently, the response of patients to these compositions is gradually reduced and no sufficient therapeutic effect can be obtained.
On the other hand, novel phenethylamine derivatives had been disclosed in WO 88/2254 as a psychotropic composition and so on. Considerable attention has been paid to these phenethylamine derivatives, because these showed the catecholaminergic activity enhancer effect (CAE effect), which is a newly discovered action to enhance the catecholamine release due to amplification of the membrane potential dependent exocytosis, and which is different from the above releasing action by displacing catecholamine from their storage [Life Sci., 58, 945-952 (1996)]. However, these compounds did not settle the increase of the intersignal reaction that is an indicator of abnormal behavior in the conditioned avoidance task. Therefore, the development of highly selective CAE drug has been required. Then, we had developed novel compounds enhancing catecholamine release by CAE effect, and found them useful as a psychotropic composition, antidepressants, composition for the treatment of Parkinsons""s disease and/or of Alzheimer""s disease (patent application No. JP 9/247445).
Organic amine compounds in patent application No. JP 9/247445 are racemic compounds consisting of two equimolar amount of optical isomers (enantiomers), because they have an asymmetric carbon. As for racemic compounds that are mixtures of optical isomers, one of a pair generally showed higher activity than the other. Therefore, optical resolutions of isomers were tried by using the methods preparing the diastereomer salts or derivatives. However, it turned out not to be easy to carry out the optical resolution of racemic compounds in patent application No. JP 9/247445, because of their own flexible substituents.
The purpose of the invention is to obtain the respective optical isomers from organic amine compounds in patent application No. JP 9/247445 by means of the optical resolution, and to find useful remedies from the optical isomers by pharmacological screening. Furthermore, pharmaceutical compositions such as a psychotropic composition, antidepressants, composition for treating Parkinson""s disease, and/or Alzheimer""s disease, are also the purpose of the invention.
Following the invention, above purpose of the invention is achieved by novel optically pure (xe2x88x92)-1-(benzofuran-2-yl)-2-propylaminopentane as represented by the following formula and the pharmaceutically acceptable acid salts thereof, and a pharmaceutically acceptable carrier. 
The inventors have examined optical resolution to obtain optically pure isomers from racemic compounds that were psychotropic composition, antidepressants, composition for treating Parkinson""s disease and/or Alzheimer""s disease. Various methods were tried to obtain optically active compound from the compounds in patent application No. JP 9/247445, and at last, optical resolution was achieved by high performance liquid chromatography method using a chiral column described in example 1. This novel optically active compound or its acid salts were found to show psychotropic and antidepressant actions by excellent CAE effects. Particularly (xe2x88x92)-1-(benzofuran-2-yl)-2-propylaminopentane or the pharmaceutically acceptable acid salts thereof were found to show high activity, and the invention was completed.
No one has expected whether among these compounds (xe2x88x92)-1-(benzofuran-2-yl)-2-propylaminopentane substantially including no (+)-form showed excellent CAE effect, or not. Because a lot of compounds disclosed in patent application No. JP 9/247445, including 1-(benzofuran-2-yl)-2-propylaminopentane, are not open to the public now, and the method of optical resolution for these racemic organic amine compounds and pharmacological actions of optical isomer also have been unknown.